The goals are to clarify the genetics and neurobiology of Huntington's Disease. These goals will be accomplished through administrative and clinical cores which will facilitate collaborations and maintain a well-characterized research population. The aims of the project are to predict the risk of H.D. in at-risk individuals; to use recombinant DNA and restriction enzyme techniques to investigate linkage in large families available in Maryland in order to study genetic heterogeneity in H.D.; to study receptor abnormalities in H.D. with positron emission tomography and to relate these abnormalities to studies of the neuropsychology of memory and attention, and to abnormalities of eye movements. Post-mortem material from clinically well studied cases will be used to develop a quantitative neuropathology of H.D. using autoradiographic techniques, studies of the GABA-benzodiazepine receptors and measurement of glutamate and related acidic analogs in the brains of H.D. patients. The function of the primate neustriatum will be studied in behaving primates and will be related to striatal inhomogeneities. Results of this research will clarify the pathogenetic mechanisms in order to formulate hypotheses for a rationale treatment and preventative measures for this tragic disease.